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Phase I/II Randomized Trial of Sorafenib and Bevacizumab as First-Line Therapy in Patients With Locally Advanced or Metastatic Hepatocellular Carcinoma


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Liver Cancer

Thank you

Trial Information

Phase I/II Randomized Trial of Sorafenib and Bevacizumab as First-Line Therapy in Patients With Locally Advanced or Metastatic Hepatocellular Carcinoma


OBJECTIVES:

Primary

- Determine the maximum tolerated dose of bevacizumab in combination with sorafenib
tosylate in patients with locally advanced or metastatic hepatocellular carcinoma.
(Phase I closed to accrual as of 11/03/2010)

- Determine time to progression in these patients. (Phase II)

Secondary

- Determine the safety of this regimen in these patients. (Phase I closed to accrual as
of 11/03/2010)

- Assess tolerability of this regimen in these patients. (Phase I closed to accrual as of
11/03/2010)

- Determine overall survival of these patients. (Phase II)

- Determine tumor response (at 6 months) in patients treated with this regimen. (Phase
II)

- Determine progression-free survival of these patients. (Phase II)

- Determine response rate in patients treated with this regimen. (Phase II)

- Assess the occurrence of adverse events in these patients. (Phase II)

Tertiary

- Determine the relationship between tumor biomarkers and circulating biomarkers of
vascular response and clinical outcome in patients treated with this regimen.

OUTLINE: This is a phase I, dose escalation study followed by a randomized phase II study.

- Phase I (closed to accrual as of 11/03/2010): Patients receive oral sorafenib tosylate
twice daily on days 1-28 and bevacizumab IV on days 1 and 15. Courses repeat every 28
days in the absence of disease progression or unacceptable toxicity.

- Phase II: Patients are stratified according to gender (female vs male), ECOG
performance status (0 vs 1), and Child-Pugh class (A vs B7). Patients are randomized to
1 of 2 treatment arms.

- Arm I: Patients receive oral sorafenib tosylate on days 1-28 twice daily and
bevacizumab IV on days 1 and 15.

- Arm II: Patients receive oral sorafenib tosylate twice daily on days 1-28. In both
arms, courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.

Blood samples are collected periodically for analysis of circulating endothelial cells and
circulating endothelial progenitor cells and angiogenic proteins in plasma by ELISA.

After completion of study treatment, patients are followed for 3 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed hepatocellular carcinoma

- Locally advanced or metastatic disease that is not amenable to treatment with
surgery or to orthotopic liver transplant

- Child Pugh class A or B7 disease

- Measurable disease

- No mixed cholangiocarcinoma/hepatocellular carcinoma

- No current or previously resected brain metastases

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- Life expectancy ≥ 3 months

- ANC ≥ 1,200/mm³

- Platelet count ≥ 75,000/mm³

- Hemoglobin ≥ 9.0 g/dL

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST ≤ 5 times ULN

- Alkaline phosphatase ≤ 5 times ULN

- Urine protein ≤ 1+ by urine protein:creatinine ratio OR 24-hour urine protein < 1 g

- QTc interval ≤ 500 msec on baseline EKG

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 2 weeks after
sorafenib tosylate and 6 months after bevacizumab

- None of the following risk factors for decreased LVEF:

- Prior treatment with anthracyclines

- History of myocardial infarction within the past 12 months

- No uncontrolled hypertension (defined as systolic blood pressure [BP] > 150 mm Hg or
diastolic BP > 100 mm Hg) despite optimal medical management

- No New York Heart Association class III-IV congestive heart failure

- No cardiac ventricular arrhythmias requiring antiarrhythmic therapy

- No history of hypertensive crisis or hypertensive encephalopathy

- No cardiac ventricular arrhythmia requiring anti-arrhythmic therapy within the past 6
months

- None of the following within the past 6 months:

- Transient ischemic attack

- Cerebrovascular accident

- Unstable angina or angina

- Clinically significant peripheral artery disease (i.e., claudication in less
than one block) or any other arterial thrombotic event

- Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess

- Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or
recent peripheral arterial thrombosis

- No active or recent history of hemoptysis (≥ ½ teaspoon of bright red blood per
episode) within the past 30 days

- No evidence of bleeding diathesis (greater than normal risk of bleeding) or
coagulopathy (in the absence of therapeutic anticoagulation)

- No significant traumatic injury within the past 4 weeks

- No serious or non-healing wound, ulcer, or bone fracture

- No uncontrolled intercurrent illness, including, but not limited to, ongoing or
active infection, or psychiatric illness/social situations that would limit
compliance with study requirements

- No other active malignancy within the past 3 years, except nonmelanotic skin cancer
or carcinoma in situ of the cervix

- No comorbid systemic illnesses or other severe concurrent disease which, in the
judgment of the investigator, would make the patient inappropriate for entry into
this study or interfere significantly with the proper assessment of safety and
toxicity of the prescribed regimens

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to bevacizumab or sorafenib tosylate

PRIOR CONCURRENT THERAPY:

- No prior systemic chemotherapy regimens for hepatocellular carcinoma

- No prior external beam radiation to the primary site

- No prior central thoracic radiation therapy (RT), including RT to the heart

- No prior radiation (if given for another malignancy) to ≥ 25% of the bone marrow

- At least 6 weeks since prior chemoembolization, radioembolization, radiofrequency
ablation, or other local ablative therapies

- More than 4 weeks since prior biologic, hormonal, or immune therapy

- More than 4 weeks since prior and no concurrent major surgical procedure or open
biopsy

- More than 7 days since prior core biopsy or other minor surgical procedure (placement
of a vascular access device allowed)

- No concurrent investigational agent which would be considered as a treatment for the
primary neoplasm

- No concurrent anticoagulants, except low-dose warfarin or heparin for deep venous
thrombosis prophylaxis

- No other concurrent treatment for prior malignancy (other than hormonal therapy)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose

Safety Issue:

No

Principal Investigator

Steven R. Alberts, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic

Authority:

United States: Federal Government

Study ID:

CDR0000637866

NCT ID:

NCT00867321

Start Date:

April 2009

Completion Date:

Related Keywords:

  • Liver Cancer
  • adult primary hepatocellular carcinoma
  • advanced adult primary liver cancer
  • localized unresectable adult primary liver cancer
  • recurrent adult primary liver cancer
  • Liver Neoplasms
  • Carcinoma, Hepatocellular

Name

Location

Mayo Clinic ScottsdaleScottsdale, Arizona  85259
Mayo Clinic Cancer CenterRochester, Minnesota  55905
CCOP - WichitaWichita, Kansas  67214-3882
Hurley Medical CenterFlint, Michigan  48503
CCOP - Illinois Oncology Research AssociationPeoria, Illinois  61602
CCOP - Iowa Oncology Research AssociationDes Moines, Iowa  50309-1016
CCOP - Metro-MinnesotaSaint Louis Park, Minnesota  55416
Aurora Presbyterian HospitalAurora, Colorado  80012
Boulder Community HospitalBoulder, Colorado  80301-9019
Penrose Cancer Center at Penrose HospitalColorado Springs, Colorado  80933
CCOP - Colorado Cancer Research ProgramDenver, Colorado  80224-2522
Porter Adventist HospitalDenver, Colorado  80210
Presbyterian - St. Luke's Medical CenterDenver, Colorado  80218
St. Joseph HospitalDenver, Colorado  80218
Rose Medical CenterDenver, Colorado  80220
Swedish Medical CenterEnglewood, Colorado  80110
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical CenterGrand Junction, Colorado  81502
Sky Ridge Medical CenterLone Tree, Colorado  80124
Hope Cancer Care Center at Longmont United HospitalLongmont, Colorado  80502
St. Mary - Corwin Regional Medical CenterPueblo, Colorado  81004
North Suburban Medical CenterThornton, Colorado  80229
Mercy Medical Center - Sioux CitySioux City, Iowa  51104
Siouxland Hematology-Oncology Associates, LLPSioux City, Iowa  51101
St. Luke's Regional Medical CenterSioux City, Iowa  51104
CCOP - Michigan Cancer Research ConsortiumAnn Arbor, Michigan  48106
Saint Joseph Mercy Cancer CenterAnn Arbor, Michigan  48106-0995
Oakwood Cancer Center at Oakwood Hospital and Medical CenterDearborn, Michigan  48123-2500
Genesys Hurley Cancer InstituteFlint, Michigan  48503
Van Elslander Cancer Center at St. John Hospital and Medical CenterGrosse Pointe Woods, Michigan  48236
Sparrow Regional Cancer CenterLansing, Michigan  48912-1811
St. John Macomb HospitalWarren, Michigan  48093
MeritCare BemidjiBemidji, Minnesota  56601
Fairview Ridges HospitalBurnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy HospitalCoon Rapids, Minnesota  55433
Duluth Clinic Cancer Center - DuluthDuluth, Minnesota  55805-1983
CCOP - DuluthDuluth, Minnesota  55805
Miller - Dwan Medical CenterDuluth, Minnesota  55805
Fairview Southdale HospitalEdina, Minnesota  55435
Mercy and Unity Cancer Center at Unity HospitalFridley, Minnesota  55432
Hutchinson Area Health CareHutchinson, Minnesota  55350
Minnesota Oncology Hematology, PA - MaplewoodMaplewood, Minnesota  55109
HealthEast Cancer Care at St. John's HospitalMaplewood, Minnesota  55109
Hennepin County Medical Center - MinneapolisMinneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern HospitalMinneapolis, Minnesota  55407
Hubert H. Humphrey Cancer Center at North Memorial Outpatient CenterRobbinsdale, Minnesota  55422-2900
St. Francis Cancer Center at St. Francis Medical CenterShakopee, Minnesota  55379
Park Nicollet Cancer CenterSt. Louis Park, Minnesota  55416
Regions Hospital Cancer Care CenterSt. Paul, Minnesota  55101
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
Minnesota Oncology Hematology, PA - WoodburyWoodbury, Minnesota  55125
MeritCare BroadwayFargo, North Dakota  58122
CCOP - MeritCare HospitalFargo, North Dakota  58122
Natalie Warren Bryant Cancer Center at St. Francis HospitalTulsa, Oklahoma  74136
Geisinger Medical Group - Scenery ParkState College, Pennsylvania  16801
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical CenterWilkes-Barre, Pennsylvania  18711
Sanford Cancer Center at Sanford USD Medical CenterSioux Falls, South Dakota  57117-5039
Medical X-Ray Center, PCSioux Falls, South Dakota  57105
Rapid City Regional HospitalRapid City, South Dakota  57709
Methodist Medical Center of IllinoisPeoria, Illinois  61636
CCOP - Montana Cancer ConsortiumBillings, Montana  59101
Hinsdale, Illinois  60521
CCOP - Grand RapidsGrand Rapids, Michigan  49503
John Stoddard Cancer Center at Iowa Methodist Medical CenterDes Moines, Iowa  50309
Via Christi Cancer Center at Via Christi Regional Medical CenterWichita, Kansas  67214
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
Green Bay Oncology, Limited - EscanabaEscanaba, Michigan  49431
Dickinson County Healthcare SystemIron Mountain, Michigan  49801
St. Mary's Hospital Medical Center - Green BayGreen Bay, Wisconsin  54303
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54301-3526
Green Bay Oncology, Limited at St. Mary's HospitalGreen Bay, Wisconsin  54303
Bay Area Cancer Care Center at Bay Area Medical CenterMarinette, Wisconsin  54143
Green Bay Oncology, Limited - Oconto FallsOconto Falls, Wisconsin  54154
Green Bay Oncology, Limited - Sturgeon BaySturgeon Bay, Wisconsin  54235
North Colorado Medical CenterGreeley, Colorado  80631
McKee Medical CenterLoveland, Colorado  80539
Battle Creek Health System Cancer Care CenterBattle Creek, Michigan  49017
Munson Medical CenterTraverse City, Michigan  49684
Hematology-Oncology Centers of the Northern Rockies - BillingsBillings, Montana  59101
St. Peter's HospitalHelena, Montana  59601
Kalispell Regional Medical CenterKalispell, Montana  59901
Glacier Oncology, PLLCKalispell, Montana  59901
Montana Cancer Center at St. Patrick Hospital and Health Sciences CenterMissoula, Montana  59802
Montana Cancer Specialists at Montana Cancer CenterMissoula, Montana  59802
Butterworth Hospital at Spectrum HealthGrand Rapids, Michigan  49503-2560
Geisinger Cancer Institute at Geisinger HealthDanville, Pennsylvania  17822-0001
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical CenterHartford, Connecticut  06105
St. Joseph Medical CenterBloomington, Illinois  61701
Graham HospitalCanton, Illinois  61520
Memorial HospitalCarthage, Illinois  62321
Eureka Community HospitalEureka, Illinois  61530
Mason District HospitalHavana, Illinois  62644
McDonough District HospitalMacomb, Illinois  61455
BroMenn Regional Medical CenterNormal, Illinois  61761
Community Cancer CenterNormal, Illinois  61761
Community Hospital of OttawaOttawa, Illinois  61350
Oncology Hematology Associates of Central Illinois, PC - OttawaOttawa, Illinois  61350
Cancer Treatment Center at Pekin HospitalPekin, Illinois  61554
Oncology Hematology Associates of Central Illinois, PC - PeoriaPeoria, Illinois  61615
OSF St. Francis Medical CenterPeoria, Illinois  61637
Proctor HospitalPeoria, Illinois  61614
Illinois Valley Community HospitalPeru, Illinois  61354
Perry Memorial HospitalPrinceton, Illinois  61356
Bettendorf, Iowa  52722
John Stoddard Cancer Center at Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
Medical Oncology and Hematology Associates at John Stoddard Cancer CenterDes Moines, Iowa  50309
Medical Oncology and Hematology Associates at Mercy Cancer CenterDes Moines, Iowa  50314
Mercy Cancer Center at Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
Medical Oncology and Hematology Associates - West Des MoinesWest Des Moines, Iowa  50266
Cancer Center of Kansas, PA - Dodge CityDodge City, Kansas  67801
Mecosta County Medical CenterBig Rapids, Michigan  49307
Bismarck Cancer CenterBismarck, North Dakota  58501
Holy Family Memorial Medical Center Cancer Care CenterManitowoc, Wisconsin  54221-1450
Welch Cancer Center at Sheridan Memorial HospitalSheridan, Wyoming  82801
St. Anthony Central HospitalDenver, Colorado  80204-1335
Exempla Lutheran Medical CenterWheat Ridge, Colorado  80033
Missouri Baptist Cancer CenterSt. Louis, Missouri  63131
Cancer Center of Kansas, PA - ChanuteChanute, Kansas  66720
Cancer Center of Kansas, PA - El DoradoEl Dorado, Kansas  67042
Cancer Center of Kansas - Fort ScottFort Scott, Kansas  66701
Cancer Center of Kansas-IndependenceIndependence, Kansas  67301
Cancer Center of Kansas, PA - KingmanKingman, Kansas  67068
Lawrence Memorial HospitalLawrence, Kansas  66044
Cancer Center of Kansas, PA - LiberalLiberal, Kansas  67905
Cancer Center of Kansas, PA - NewtonNewton, Kansas  67114
Cancer Center of Kansas, PA - ParsonsParsons, Kansas  67357
Cancer Center of Kansas, PA - PrattPratt, Kansas  67124
Cancer Center of Kansas, PA - SalinaSalina, Kansas  67401
Cancer Center of Kansas, PA - WellingtonWellington, Kansas  67152
Cancer Center of Kansas, PA - WichitaWichita, Kansas  67214
Associates in Womens Health, PA - North ReviewWichita, Kansas  67208
Cancer Center of Kansas, PA - Medical Arts TowerWichita, Kansas  67208
Cancer Center of Kansas, PA - WinfieldWinfield, Kansas  67156
Foote Memorial HospitalJackson, Michigan  49201
St. Mary Mercy HospitalLivonia, Michigan  48154
St. Joseph Mercy OaklandPontiac, Michigan  48341-2985
Mercy Regional Cancer Center at Mercy HospitalPort Huron, Michigan  48060
Seton Cancer Institute at Saint Mary's - SaginawSaginaw, Michigan  48601
Fergus Falls Medical Group, PAFergus Falls, Minnesota  56537
Willmar Cancer Center at Rice Memorial HospitalWillmar, Minnesota  56201
Billings Clinic - DowntownBillings, Montana  59107-7000
Bozeman Deaconess Cancer CenterBozeman, Montana  59715
St. James Healthcare Cancer CareButte, Montana  59701
Great Falls Clinic - Main FacilityGreat Falls, Montana  59405
Sletten Cancer Institute at Benefis HealthcareGreat Falls, Montana  59405
Northern Montana HospitalHavre, Montana  59501
Kalispell Medical Oncology at KRMCKalispell, Montana  59901
Geisinger Hazleton Cancer CenterHazleton, Pennsylvania  18201
Rocky Mountain OncologyCasper, Wyoming  82609
Mid Dakota Clinic, PCBismarck, North Dakota  58501
Lacks Cancer Center at Saint Mary's Health CareGrand Rapids, Michigan  49503
Metro Health HospitalGrand Rapids, Michigan  49506
Galesburg Clinic, PCGalesburg, Illinois  61401
St. Vincent Healthcare Cancer Care ServicesBillings, Montana  59101
Illinois CancerCare - BloomingtonBloomington%, Illinois  61701
Illinois CancerCare - CantonCanton, Illinois  61520
Illinois CancerCare - CarthageCarthage, Illinois  62321
Illinois CancerCare - EurekaEureka, Illinois  61530
Illinois CancerCare - GalesburgGalesburg, Illinois  61401
Illinois CancerCare - HavanaHavana, Illinois  62644
Illinois CancerCare - Kewanee ClinicKewanee, Illinois  61443
Illinois CancerCare - MacombMacomb, Illinois  61455
Trinity Cancer Center at Trinity Medical Center - 7th Street CampusMoline, Illinois  61265
OSF Holy Family Medical CenterMonmouth, Illinois  61462
Illinois CancerCare - MonmouthMonmouth, Illinois  61462
Illinois CancerCare - Community Cancer CenterNormal, Illinois  61761
Illinois CancerCare - PekinPekin, Illinois  61603
Illinois CancerCare - PeruPeru, Illinois  61354
Illinois CancerCare - PrincetonPrinceton, Illinois  61356
Illinois CancerCare - Spring ValleySpring Valley, Illinois  61362
Mercy General Health PartnersMuskegon, Michigan  49443
Medcenter One Hospital Cancer Care CenterBismarck, North Dakota  58501
St. Alexius Medical Center Cancer CenterBismarck, North Dakota  58502
Lakeview HospitalStillwater, Minnesota  55082
Goldschmidt Cancer CenterJefferson City, Missouri  65109
Comprehensive Cancer Care, PCSaint Louis, Missouri  63141
St. Nicholas HospitalSheboygan, Wisconsin  53081